Unsolved drugs

A simmering controversy surrounds what’s still unknown about how antibiotics kill

BATTLING BACK Antibiotics such as penicillin attack a bacterium’s cell wall, bursting it (left, shown next to an intact Staphylococcus aureus cell in false color). Some studies suggest that antibiotics also trigger other kinds of damage that could be harnessed in the battle against antibiotic resistance.

CNRI/Science Source

Penicillin attacks with a calculated strike, splitting open cell walls. Kanamycin sends a bacterium’s protein assembly line into mayhem. Ciprofloxacin dices a microbe’s DNA into a genetic hash. Like trained snipers, each of these common antibiotics seems to dispatch bacteria with a simple tactic: Target a high-profile molecule crucial to survival and, with a single, clean shot, defeat the whole cell.

For decades, this notion of how antibiotics kill has guided the design and deployment of drugs that have saved countless lives. Since scientists introduced penicillin in the 1940s, antibiotics have tamed some of the most deadly microbes into mild nuisances. Bacterial infections that cause tuberculosis, pneumonia and diarrhea, the three leading killers in the United States a century ago, have become curable or rare in the developed world.

But after myriad clinical victories, some scientists are questioning what we really know about the modus operandi of these

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